Drugs that kill or inhibit the sexual stages of Plasmodium in order to prevent transmission are important components of malaria control programmes. Reducing gametocyte carriage is central to the control of Plasmodium falciparum transmission as infection can result in extended periods of gametocytaemia. Unfortunately the number of drugs with activity against gametocytes is limited. Primaquine is currently the only licensed drug with activity against the sexual stages of malaria parasites and its use is hampered by safety concerns. This shortcoming is likely the result of the technical challenges associated with gametocyte studies together with the focus of previous drug discovery campaigns on asexual parasite stages. However recent emphasis on malaria eradication has resulted in an upsurge of interest in identifying compounds with activity against gametocytes. This review examines the gametocytocidal properties of currently available drugs as well as those in the development pipeline and examines the prospects for discovery of new anti-gametocyte compounds.

Drug development for paediatric applications entails a number of challenges, such as the wide age spectrum covered – from birth to adolescence – and developmental changes in physiology during biological maturation that influence the efficacy and toxicity of drugs. Safe and efficacious antiparasitic drugs for children are of pivotal importance given the large proportion of burden attributable to parasitic diseases in this age group, and growing efforts to administer, as widely as possible, antiparasitic drugs to at-risk populations, such as infants and school-aged children, often without prior diagnosis. The purpose of this review is to investigate whether antiparasitic drugs have been adequately studied for use in paediatrics. We approached this issue through a systematic review using PubMed and the Cochrane Central Register of Trials covering a period of 10 years and 8 months until the end of August 2010 to identify trials that investigated efficacy, safety and pharmacokinetic (PK) parameters of antiparasitic drugs for paediatrics. Overall, 269 clinical drug trials and 17 PK studies met our inclusion criteria. Antimalarial drugs were the most commonly studied medicines (82·6%). Most trials were carried out in Africa and children aged 2–11 years were the age group most often investigated. Additionally, we critically examined available drug formulations for anthelminthics and identified a number of shortcomings that are discussed. Finally, we shed new light on current proposals to expand ‘preventive chemotherapy’ to preschool-aged children and emphasise that new research, including risk-benefit analyses, are needed before such a strategy can be adopted more widely.

In the Central African Republic (CAR) malaria is a major public health problem and hampers socioeconomic development. It accounts for 40 percent of complaints and 10 percent of deaths in health facilities (15;17). Pregnant women, who make up 4 percent of the population, and children under 5 years of age, who represent 17.3 percent, are the groups most vulnerable to malaria owing to their low levels of immunity.

Malaria is a major public health problem in Burkina Faso. Statistics from health facilities in 2006 show that 40.1 percent of medical consultations, 53.4 percent of hospital admissions, and 45.8 percent of deaths are malaria related (2). Malaria among children under 5 years of age accounted for 46 percent of all cases in 2004, 49 percent in 2005 and 48 percent in 2006. In the same age group, malaria was the cause of 66.4 percent of deaths in 2004, 62.0 percent in 2005 and 62.7 percent in 2006.

Malaria in Ethiopia is one of the leading causes of death (21.8 percent), consultation in outpatient departments (17.8 percent) and hospital admissions (14.1 percent) (2;14). To overcome this problem, the Malaria Control Program (Federal Ministry of Health) has designed a community-based malaria treatment approach that played key roles in malaria epidemic control and community mobilization as well as vector control operations. In this approach, Community Health Workers (CHWs) and Village Malaria Workers, volunteers selected by community and trained on malaria diagnosis and treatment as well as indoor residual spray for few days (16). However, sustainability of this approach has been a challenge to the malaria control program. Thus, institutional arrangements in which every Kebele (the smallest administrative unit of 5,000 people) has a health post staffed by two Health Extension Workers (HEW) as part of the country's health system is a breakthrough to strengthen malaria control. A study has shown that more than half of the patients with fever visit CHWs and private health facility services (4).

Malaria is the major cause of illness in Cameroon, responsible for 40 percent of medical consultations. For this reason, the Head of State along with his African Union peers in April 2000 and 2006 undertook to achieve universal access to malaria control interventions, including effective treatment (10;12). Uneven distribution of health services, especially in rural areas, and high poverty rates make health care and drugs inaccessible or unaffordable (14;16). Therefore, the World Health Organization recommends building comprehensive mechanisms grounded on relevant social and community organizations, including the private sector, to improve access to care for vulnerable populations (22;23). Accordingly, the strategic plan to fight malaria in Cameroon, endorsed by the National Committee to Roll Back Malaria, recommends home-based management of malaria (HMM) to improve access and reduce delays in treatment (12).

The World Health Organization (WHO) since June 1998 has advocated for the use of artemisinin-based combination therapies (ACTs) in countries where Plasmodium falciparum malaria is resistant to traditional antimalarial therapies such as chloroquine, sulfadoxine-pyrimethamine, and amodiaquine (19;22). In 2006, WHO released evidence-based guidelines for the treatment of malaria backed by findings from various scientific studies (21). During the period between 2002 and 2006, all the five East African states Tanzania, Kenya, Uganda, Rwanda, and Burundi changed their national antimalarial treatment policies to use ACTs as first-line treatments for uncomplicated falciparum malaria and commenced with deployment of the drugs in the state-managed health facilities (12–15). To scale up the use of ACTs in the East African region to combat malaria and speed up progress toward the sixth Millennium Development Goal, a combination of delivery, financial, and governance arrangements tailored to national or subnational contexts needs to be considered.

Malaria is a major cause of morbidity and mortality in Mozambique. Approximately 6 million cases are reported each year. Malaria accounts for approximately 40 percent of all outpatient visits and 60 percent of pediatric hospital admissions. It is the leading cause of death among children admitted to pediatric services. Malaria transmission takes place year round with a seasonal peak extending from December to April. More than 18.5 million people in Mozambique are considered to be at-risk of malaria, including an estimated 3.6 million children less than 5 years old and almost 1 million pregnant women (13). The Presidential Malaria Initiative (PMI) -supported Malaria Indicator Survey, conducted in 2007, found the national prevalence of malaria parasitemia among children 6 to 59 months old to be 38.5 percent, with a range by province from 60.4 percent in Nampula to less than 10 percent in Maputo. Among pregnant women, the parasite prevalence was 16.3 percent, with 30.1 percent of women in their first pregnancy demonstrating parasites on blood slides (11).

The present report deals with the status of hepatic and splenic glutathione-S-transferase (GST) activities in mice during experimental infection with Plasmodium yoelii nigeriensis and subsequent treatment of infected mice with mefloquine (Mf) and menadione (Md). The infection caused significant decline in the hepatic and splenic glutathione-S-transferase (GST) activities of albino and db/+ mice. The decline was observed in the levels of both cytosolic and microsomal GST(s) of liver and spleen in both types of mice. Intraperitoneal administration of mefloquine at a dose of 5 mg/kg and menadione at a dose of 100 mg/kg, twice daily from day 1 p.i. (day 0) until day 10, caused restoration in the levels of hepatic as well as splenic GST(s), albeit to varying degrees. Mf was able to suppress parasitaemia by day 5 in the case of albino mice and by day 3 in the case of db/+ mice but was unable to cure both types of mice completely. On the other hand, Md caused a delay in maturation of infection in both cases, but could not cure the mice.

Blood schizontocidal activity of 10 selected cis-fused cyclopenteno-1,2,4-trioxanes (namely Fenozan compound nos 6, 7, 11, 27, 32, 39, 44, 45, 48 and 51) have been re-investigated to establish their curative doses against the multidrug-resistant Plasmodium yoelii nigeriensis strain, which is lethal in Swiss mice. Freshly prepared formulations of these compounds prepared either in neutral groundnut (peanut) oil or in dimethyl sulfoxide (DMSO)-Tween-water, were compared for their antimalarial activity. Only 2 compounds, namely Fenozan derivatives 11 and 45, formulated in neutral groundnut oil for oral administration, showed highest activity with 100% cure rate in MDR P. yoelii nigeriensis-infected mice, while the DMSO-Tween-water formulations were inactive. Fenozan-48 produced 72·2% cure, when administered orally in groundnut oil (formulation) while its DMSO-Tween formulation was inactive. In the case of Fenozan 7, the oil and DMSO-Tween formulations produced 92·3 and 76·0% cures respectively. Fenozan derivatives nos 6, 27, 32, 39, 44 and 51 were not protective either in groundnut oil or DMSO-Tween oral formulations. The present study has applied more rigorous criteria for selection of active compounds, and has identified the 3,3-spirocyclopentane derivative Fenozan 11, and the 3,3-spirohydropyran derivative Fenozan 45, as potential blood schizontocides which can completely eliminate multidrug-resistant malaria infection in mice. Both these compounds are candidates for pre-clinical development. The present study advocates the preferred use of an oil vehicle for oral evaluation of potential antimalarial trioxanes/fenozans instead of the DMSO formulation, which gives inferior curative efficacy.

Studies of population genetic structure of parasites can be used to infer which parasite genes are under selection. Here, the population structure of 4 genes associated with drug resistance of Plasmodium falciparum (the chloroquine resistance transporter, pfcrt, dihydrofolate reductase, dhfr, dihydropteroate synthase, dhps, and multi-drug resistance, pfmdr-1) were examined in parasite populations in 3 villages in eastern Sudan and in an urban area of Khartoum, the capital. In order to differentiate the effects of drug selection from neutral influences on population structure, parasites were also genotyped for 3 putatively neutral microsatellite loci (polyα, TA81 and pfg377), and for 2 antigenic loci that are either under balancing selection or neutral, merozoite surface protein 1 and 2, (MSP-1 and MSP-2). Cross-sectional surveys were carried out during the peak transmission (wet) season and in the ensuing dry season. No significant variation in frequencies of MSP-1 and MSP-2 alleles was seen among villages in the eastern region and between the villages and Khartoum, nor between the wet and dry season. However, the drug resistance genes, pfmdr-1, pfcrt and dhfr and to a lesser extent the microsatellite loci showed high FST values when comparing villages with Khartoum, indicating strong geographical differentiation at these loci. Moreover, variation in frequencies of the drug resistance genes, pfmdr-1, pfcrt and dhfr, was observed between the wet and dry season. These differences most probably reflect the variation in drug pressure between each region, and in drug usage between the wet and dry season in a given region.

This paper reports the comparative antimalarial efficacy of intravenous artelinate and artesunate in rats. Prior to efficacy experiments, a Plasmodium berghei–Sprague-Dawley rat model of malaria was developed, in which the clearance effects of intravenous drugs could be readily compared. In efficacy experiments, groups of P. berghei-infected rats were given 3 daily intravenous treatments of artelinate or artesunate at molar equivalent dose rates (total of 0–191·2 μmoles/kg). Artelinate was superior to artesunate in terms of clearance (100% clearance dose of 95·6 μmoles/kg (40 mg/kg) versus 191·2 μmoles/kg for AS (73·4 mg/kg)) and parasite clearance time (1·7±0·5 days for AL versus 2·7±0·5 days for AS at a dose rate of 191·2 μmoles/kg, P<0·01). No frank clinical toxicity was observed, though both artesunate and artelinate induced dose-related vascular necrosis at the site of injection. The necrosis was less severe and reversible when the drugs were administered via femoral, rather than tail/foot veins. The data suggest that the P. berghei–7-week-old Sprague-Dawley rat model of malaria is reproducible and useful for assessing the efficacy of antimalarials and that artelinate is at least as potent, and safe, as artesunate, the leading clinical treatment for severe malaria.

Eight papers were presented on topics ranging from the dissemination of drug resistance in Africa; the application of new antimalarial compounds; the basic biology of the malarial parasite; and methods for in vitro culture and its analysis, to the interaction of the malarial parasite with the infected host with particular reference to host genetic factors responsible for parasite survival.